This project will investigate the mechanisms governing the control of ventilation and respiratory pattern in humans. Previous studies in this laboratory have shown that total ventilation during exercise and various chemical stimulations is determined by the balance between the chemical drive and the natural tendency toward minimal respiratory work. The proposed research will further examine the validity of this model under other critical situations. Firstly, the ambiguous interaction between hypercapnia and exercise will be resolved by prudent determination of both isocapnic exercise response and isometabolic CO2 response. The model prediction of a multiplicative interaction will be tested. Secondly, the optimal control model will be extended to include predictions of the respiratory patterns as components of total ventilation. These predictions will be evaluated under conditions of external intervention with added dead space and mechanical loading. The results will lead to a general description of the ventilation and respiratory pattern responses under different conditions of chemical stimulation, exercise, as well as artificial or pathologic impairments of pulmonary gas exchange or respiratory mechanics.